The long term objective of this research is to elucidate the mechanism by which steroid hormones regulate uterine blood flow. The proposed research will investigate the relative contribution of changes in vessel tone and changes in vessel contractility induced by estrogen and progesterone. The specific aims, which are based on work performed in the last grant period, are designed to methodically test the following working hypothesis: Estrogen regulates tone by being converted to a catechol estrogen (CE); Progesterone regulates contractility by prompting synthesis of Alpha1-adrenergic receptors in the uterine artery; contractility is also under control of estrogen or CE via estrogenic modulation of uterine arterial norepinephrine. Pursuit of the specific aims will employ a multidisciplinary approach and will draw upon the investigator's expertise in the fields of Animal Science (Reproduction), Obstetrics/Gynecology, Immunochemistry, Endocrinology, Medicinal Chemistry and Enzymology. Although the rat andpig are the animals under study, the research results should have extensive application in human medicine. Certainly the results should help understand the mechanisms underlying pathologic conditions characterized by insufficient uterine blood flow: Infertility, abortion, intrauterine growth retardation and toxemia of pregnancy. Since a Medicinal Chemist collaborates on this study, there is an opportunity to design and synthesize the drugs needed to restore the uterine blood flow to normalcy.